PROJECT SUMMARY Recently, the Systolic Blood Pressure Intervention Trial (SPRINT) reported that more intensive blood pressure (BP) treatment (target systolic BP<120 mmHg) reduced major cardiovascular disease (CVD) by about 25% and all-cause mortality by about 27% compared to standard BP treatment (target systolic BP<140 mmHg) among hypertensive patients aged ?50 years and at high risk for CVD. SPRINT clearly answered the question ? Will lowering BP more than the currently recommended goal further reduce the risk of CVD and mortality? The next important question is how to implement a more intensive BP treatment program in real-world clinical practice, especially in populations with health disparities. Traditionally, underserved populations have benefited less from clinical research, which contributes to health disparities in the US. We propose to conduct an effectiveness-implementation hybrid trial to simultaneously test the effectiveness of a multicomponent intervention for more intensive BP treatment and the feasibility, fidelity, and sustainability of implementing the intervention in underserved patients with hypertension and at high risk for CVD in Louisiana. The Consolidated Framework for Implementation Research has been used to guide the development of the multicomponent intervention, including protocol-based treatment using the SPRINT stepped-care intensive BP management algorithm, dissemination of SPRINT study findings among patients, provider-teams, and administrators, team- based collaborative care, BP audit and feedback, home BP monitoring, and health coaching on BP medication adherence and lifestyle modification. We will collaborate with 30 Federally Qualified Health Center clinics that serve low-income populations in southeast Louisiana to conduct the proposed trial. The primary clinical outcome is the difference in the proportion of patients with systolic BP <120 mmHg between the intervention and control groups at 18 months. The secondary outcomes are the differences in mean changes of systolic and diastolic BP from baseline to 18 months, adverse effects, and quality of life. The fidelity of the intervention, measured by intensification of treatment (titration or addition of new medication) by provider-teams and adherence to medications in patients, will be the primary implementation outcome. The proposed trial, with a sample size of 30 clinics (38 patients/clinic), has 90% statistical power to detect a 15% increase in the proportion of patients with systolic BP<120 mmHg (primary clinical outcome) at a 2-sided significance level of 0.05. An intra-cluster correlation of 0.049 and a proportion of patients with intensive BP control (systolic BP <120 mmHg) of 25% in the control group are assumed based on previous experience. We will recruit 1,350 patients (45 patients/clinic) to make up for lost statistical power due to potential withdrawal. This study is very timely and has important public health and clinical implications. It will generate urgently needed data on effective, adoptable, and sustainable intervention strategies aimed at eliminating health disparities and reducing the BP-related disease burden in ethnic minority and low-income populations in the US.